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As supercapacitor (SC) technology continues to evolve, there is a growing need for electrode materials with high energy/power densities and cycling stability. However, research and development of electrode materials with such characteristics is essential for commercialization the SC. To meet this demand, the development of superior electrode materials has become an increasingly critical step. The electrochemical performance of SCs is greatly influenced by various factors such as the reaction mechanism, crystal structure, and kinetics of electron/ion transfer in the electrodes, which have been challenging to address using previously investigated electrode materials like carbon and metal oxides/sulfides. Recently, tellurium and telluride-based materials have garnered increasing interest in energy storage technology owing to their high electronic conductivity, favorable crystal structure, and excellent volumetric capacity. This review provides a comprehensive understanding of the fundamental properties and energy storage performance of tellurium- and Te-based materials by introducing their physicochemical properties. First, we elaborate on the significance of tellurides. Next, the charge storage mechanism of functional telluride materials and important synthesis strategies are summarized. Then, research advancements in metal and carbon-based telluride materials, as well as the effectiveness of tellurides for SCs, were analyzed by emphasizing their essential properties and extensive advantages. Finally, the remaining challenges and prospects for improving the telluride-based supercapacitive performance are outlined.
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The fast growth of electrochemical energy storage (EES) systems necessitates using innovative, high-performance electrode materials. Among the various EES devices, rechargeable batteries (RBs) with potential features like high energy density and extensive lifetime are well suited to meet rapidly increasing energy demands. Layered transition metal dichalcogenides (TMDs), typical two dimensional (2D) nanomaterial, are considered auspicious materials for RBs because of their layered structures and large specific surface areas (SSA) that benefit quick ion transportation. This review summarizes and highlights recent advances in TMDs with improved performance for various RBs. Through novel engineering and functionalization used for high-performance RBs, we briefly discuss the properties, characterizations, and electrochemistry phenomena of TMDs. We summarised that engineering with multiple techniques, like nanocomposites used for TMDs receives special attention. In conclusion, the recent issues and promising upcoming research openings for developing TMDs-based electrodes for RBs are discussed.
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Since the initial MXenes were discovered in 2011, several MXene compositions constructed using combinations of various transition metals have been developed. MXenes are ideal candidates for different applications in energy conversion and storage, because of their unique and interesting characteristics, which included good electrical conductivity, hydrophilicity, and simplicity of large-scale synthesis. Herein, we study the current developments in two-dimensional (2D) MXene nanosheets for energy storage and conversion technologies. First, we discuss the introduction to energy storage and conversion devices. Later, we emphasized on 2D MXenes and some specific properties of MXenes. Subsequently, research advances in MXene-based electrode materials for energy storage such as supercapacitors and rechargeable batteries is summarized. We provide the relevant energy storage processes, common challenges, and potential approaches to an acceptable solution for 2D MXene-based energy storage. In addition, recent advances for MXenes used in energy conversion devices like solar cells, fuel cells and catalysis is also summarized. Finally, the future prospective of growing MXene-based energy conversion and storage are highlighted.
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Across sub-Saharan Africa, men are less likely to know their HIV status than women, leading to later treatment initiation. Little is known about how experiences with general health services affect men's use of HIV testing. We used data from a 2019 community-representative survey of men in Malawi to understand frequency and cause of men's negative health service experiences (defined as men reporting they "would not recommend" a facility) and their association with future HIV testing. We conducted univariable and multivariable logistic regressions to determine which aspects of health facility visits were associated with would-not-recommend experiences and to determine if would-not-recommend experiences 12-24 months prior to the survey were associated with HIV testing in the 12 months prior to the survey. Among 1,098 men eligible for HIV testing in the 12 months prior to the survey, median age was 34 years; 9% of men reported at least one would-not-recommend experience, which did not differ by sociodemographics, gender norm beliefs, or HIV stigma beliefs. The factors most strongly associated with would-not-recommend experiences were cost (aOR 5.8, 95%CI 2.9-11.4), cleanliness (aOR 4.2, 95%CI 1.8-9.9), medicine availability (aOR 3.3, 95%CI 1.7-6.4), and wait times (aOR 2.7, 95%CI 1.5-5.0). Reporting a would-not-recommend experience 12-24 months ago was associated with a 59% decrease in likelihood of testing for HIV in the last 12 months (aOR 0.41; 95% CI:0.17-0.96). Dissatisfaction with general health services was strongly associated with reduced HIV testing. Coverage of high-priority screening services like HIV testing may benefit from improving overall health system quality.
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Infecciones por VIH , Prueba de VIH , Aceptación de la Atención de Salud , Humanos , Masculino , Malaui/epidemiología , Adulto , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Prueba de VIH/estadística & datos numéricos , Encuestas y Cuestionarios , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Persona de Mediana Edad , Tamizaje Masivo , Adulto Joven , Adolescente , Estigma Social , Satisfacción del Paciente/estadística & datos numéricos , Satisfacción PersonalRESUMEN
BACKGROUND: Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries: high-income countries = 600 tests/100 000 people/day; LMICs = 14 tests/100 000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. METHODS: We used Propelling Action for Testing and Treating (PATAT), an LMIC-focused agent-based model to simulate coronavirus disease 2019 (COVID-19) epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from individuals without SARS-CoV-2 and measured impact based on the number of infections averted due to test-and-isolate. RESULTS: Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires at least 200-400 tests/100 000 people/day, on average, as symptomatic testing demand is highly influenced by individuals without SARS-CoV-2. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yield the largest additional infections averted. CONCLUSIONS: Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/prevención & control , Países en Desarrollo , Prueba de COVID-19 , Prueba de Diagnóstico Rápido , ZambiaRESUMEN
Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is caused by a deficiency of the N-acetylgalactosamine-6-sulfate-sulfatase (GALNS) enzyme, leading to the accumulation of glycosaminoglycans (GAG), keratan sulfate (KS) and chondroitin-6-sulfate (C6S), mainly in cartilage and bone. This lysosomal storage disorder (LSD) is characterized by severe systemic skeletal dysplasia. To this date, none of the treatment options for the MPS IVA patients correct bone pathology. Enzyme replacement therapy with elosulfase alpha provides a limited impact on bone growth and skeletal lesions in MPS IVA patients. To improve bone pathology, we propose a novel gene therapy with a small peptide as a growth-promoting agent for MPS IVA. A small molecule in this peptide family has been found to exert biological actions over the cardiovascular system. This work shows that an AAV vector expressing a C-type natriuretic (CNP) peptide induces bone growth in the MPS IVA mouse model. Histopathological analysis showed the induction of chondrocyte proliferation. CNP peptide also changed the pattern of GAG levels in bone and liver. These results suggest the potential for CNP peptide to be used as a treatment in MPS IVA patients.
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Mucopolisacaridosis IV , Animales , Ratones , Sulfato de Queratano , Glicosaminoglicanos , Cartílago/patología , Desarrollo ÓseoRESUMEN
INTRODUCTION: Men have higher rates of morbidity and mortality across nearly all top ten causes of mortality worldwide. Much of this disparity is attributed to men's lower utilization of routine health services; however, little is known about men's general healthcare utilization in sub-Saharan Africa. METHODS: We analyze the responses of 1,116 men in a community-representative survey of men drawn from a multi-staged sample of residents of 36 villages in Malawi to identify factors associated with men's facility attendance in the last 12 months, either for men's own health (client visit) or to support the health care of someone else (caregiver visit). We conducted single-variable tests of association and multivariable logistic regression with random effects to account for clustering at the village level. RESULTS: Median age of participants was 34, 74% were married, and 82% attended a health facility in the last year (63% as client, 47% as caregiver). Neither gender norm beliefs nor socioeconomic factors were independently associated with attending a client visit. Only problems with quality of health services (adjusted odds ratio [aOR] 0.294, 95% confidence interval [CI] 0.10-0.823) and good health (aOR 0.668, 95% CI 0.462-0.967) were independently associated with client visit attendance. Stronger beliefs in gender norms were associated with caregiver visits (beliefs about acceptability of violence [aOR = 0.661, 95% CI 0.488-0.896], male sexual dominance [aOR = 0.703, 95% CI 0.505-0.978], and traditional women's roles [aOR = 0.718, 95% CI 0.533-0.966]). Older age (aOR 0.542, 95% CI 0.401-0.731) and being married (aOR 2.380, 95% CI 1.196-4.737) were also independently associated with caregiver visits. CONCLUSION: Quality of services offered at local health facilities and men's health status were the only variables associated with client facility visits among men, while harmful gender norms, not being married, and being younger were negatively associated with caregiver visits.
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Cuidadores , Hombres , Femenino , Instituciones de Salud , Humanos , Malaui , Masculino , Aceptación de la Atención de SaludRESUMEN
Adeno-associated virus (AAV) vector-based therapies can effectively correct some disease pathology in murine models with mucopolysaccharidoses. However, immunogenicity can limit therapeutic effect as immune responses target capsid proteins, transduced cells, and gene therapy products, ultimately resulting in loss of enzyme activity. Inherent differences in male versus female immune response can significantly impact AAV gene transfer. We aim to investigate sex differences in the immune response to AAV gene therapies in mice with mucopolysaccharidosis IVA (MPS IVA). MPS IVA mice, treated with different AAV vectors expressing human N-acetylgalactosamine 6-sulfate sulfatase (GALNS), demonstrated a more robust antibody response in female mice resulting in subsequent decreased GALNS enzyme activity and less therapeutic efficacy in tissue pathology relative to male mice. Under thyroxine-binding globulin promoter, neutralizing antibody titers in female mice were approximately 4.6-fold higher than in male mice, with GALNS enzyme activity levels approximately 6.8-fold lower. Overall, male mice treated with AAV-based gene therapy showed pathological improvement in the femur and tibial growth plates, ligaments, and articular cartilage as determined by contrasting differences in pathology scores compared to females. Cardiac histology revealed a failure to normalize vacuolation in females, in contrast, to complete correction in male mice. These findings promote the need for further determination of sex-based differences in response to AAV-mediated gene therapy related to developing treatments for MPS IVA.
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Condroitinsulfatasas , Mucopolisacaridosis , Mucopolisacaridosis IV , Humanos , Femenino , Ratones , Masculino , Animales , Globulina de Unión a Tiroxina/genética , Globulina de Unión a Tiroxina/metabolismo , Modelos Animales de Enfermedad , Caracteres Sexuales , Proteínas de la Cápside/genética , Terapia Genética , Anticuerpos Neutralizantes/uso terapéutico , Expresión Génica , Condroitinsulfatasas/genéticaRESUMEN
OBJECTIVES: Universal Test and Treat (UTT) strategies are being adopted across sub-Saharan Africa based on clinical benefits to morbidity and mortality and to attain targets of the Joint United Nations Programme on HIV/AIDS (UNAIDS). Universal Test and Treat is expected to change the client population at clinics, due to more asymptomatic HIV clients initiating antiretroviral therapy (ART). We assessed the impact of UTT on client appointment adherence at 14 government-managed health facilities in Eswatini's public sector health system. METHODS: We assessed the impact of UTT on client adherence to appointment schedules from 2014 to 2017 in a stepped-wedge trial. Repeated measures analysis was used to assess adherence to each scheduled appointment (primary definition: presenting for care within 7 days after the scheduled appointment), adjusting for time, age, sex, stage, marital status, ART status and facility. RESULTS: Among 3354 clients (62.1% female; 57.4% < 35 years), a median (interquartile range) of 10 (6-15) appointments were scheduled during follow-up. In a multivariable-adjusted model, appointment adherence was significantly greater in clients who were female [odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.25-1.52], older (e.g. 40 to < 50 years vs. < 20 years; OR = 1.45, 95% CI: 1.00-2.09), married (OR = 1.31, 95% CI: 1.19-1.44), had lower WHO stage at study enrolment (1-2 vs. 3-4: OR = 1.26, 95% CI: 1.13-1.41), and were currently on ART (OR = 3.55, 95% CI: 2.62-4.82). However, UTT strategy was not significantly associated with client adherence to scheduled appointments (OR = 1.02, 95% CI: 0.72-1.45). CONCLUSIONS: Despite transitioning to UTT, there was no change in visit adherence, a reassuring finding given the large volume of clients currently being initiated at earlier stages of HIV.
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Fármacos Anti-VIH , Infecciones por VIH , Adulto , Fármacos Anti-VIH/uso terapéutico , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Naciones Unidas , Adulto JovenRESUMEN
OBJECTIVE: To determine how often men in Malawi attend health facilities and if testing for human immunodeficiency virus (HIV) is offered during facility visits. METHODS: We conducted a cross-sectional, community-representative survey of men (15-64 years) from 36 villages in Malawi. We excluded men who ever tested HIV-positive. Primary outcomes were: health facility visits in the past 12 months (for their own health (client visit) or to support the health services of others (guardian visit)); being offered HIV testing during facility visits; and being tested that same day. We disaggregated all results by HIV testing history: tested ≤ 12 months ago, or in need of testing (never tested or tested > 12 months before). FINDINGS: We included 1116 men in the analysis. Mean age was 34 years (standard deviation: 13.2) and 55% (617/1116) of men needed HIV testing. Regarding facility visits, 82% (920/1116) of all men and 70% (429/617) of men in need of testing made at least one facility visit in the past 12 months. Men made a total of 1973 visits (mean two visits): 39% (765/1973) were as guardians and 84% (1657/1973) were to outpatient departments. Among men needing HIV testing, only 7% (30/429) were offered testing during any visit. The most common reason for not testing was not being offered services (37%; 179/487). CONCLUSION: Men in Malawi attend health facilities regularly, but few of those in need of HIV testing are offered testing services. Health screening services should capitalize on men's routine visits to outpatient departments as clients and guardians.
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Infecciones por VIH/diagnóstico , Instituciones de Salud/estadística & datos numéricos , Tamizaje Masivo/estadística & datos numéricos , Adolescente , Adulto , Estudios Transversales , Femenino , Infecciones por VIH/epidemiología , Humanos , Malaui/epidemiología , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Embarazo , Adulto JovenRESUMEN
Cryptosporidium is a water-borne zoonotic parasite worldwide, usually found in lakes and rivers contaminated with sewage and animal wastes, causing outbreaks of cryptosporidiosis. In this study, 300 water samples were collected from four designated places of flood-affected district Nowshera consist of different water sources to find out the prevalence of Cryptosporidium via polymerase chain reaction (PCR). The overall prevalence of Cryptosporidium was 30.33% (91/300) with more prevalent 44% in drain water and low 5% in bore/tube well water. The prevalence in open well and tap water was recorded 33% and 20%, respectively. The highest prevalence was recorded in summer (June-September). The result of this study ensures enormous contamination of drinking water that requires appropriate treatment, cleaning and filtration to provide safe drinking water. Preventing water-borne disease and proper treatment of water supplies is essential to public health.
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Cryptosporidium , Monitoreo del Ambiente , Inundaciones , Agua , Cryptosporidium/genética , Pakistán , Agua/parasitologíaRESUMEN
Immediate initiation of antiretroviral therapy (ART) for all people living with HIV has important health benefits but implications for the economic aspects of patients' lives are still largely unknown. This stepped-wedge cluster-randomized controlled trial aimed to determine the causal impact of immediate ART initiation on patients' healthcare expenditures in Eswatini. Fourteen healthcare facilities were randomly assigned to transition at one of seven time points from the standard of care (ART eligibility below a CD4 count threshold) to the immediate ART for all intervention (EAAA). 2261 patients living with HIV were interviewed over the study period to capture their past-year out-of-pocket healthcare expenditures. In mixed-effects regression models, we found a 49% decrease (RR 0.51, 95% CI 0.36, 0.72, p < 0.001) in past-year total healthcare expenditures in the EAAA group compared to the standard of care, and a 98% (RR 0.02, 95% CI 0.00, 0.02, p < 0.001) decrease in spending on private and traditional healthcare. Despite a higher frequency of HIV care visits for newly initiated ART patients, immediate ART initiation appears to have lowered patients' healthcare expenditures because they sought less care from alternative healthcare providers. This study adds an important economic argument to the World Health Organization's recommendation to abolish CD4-count-based eligibility thresholds for ART.
RESUMEN: El inicio inmediato de la terapia antirretroviral (TAR) para todas las personas que viven con VIH tiene importantes beneficios para la salud, pero aún se desconocen las implicaciones en el aspecto económico. Este ensayo controlado aleatorizado por clústers (CRT por sus siglas en inglés) por grupos en distintas etapas pretende determinar el impacto del inicio inmediato de la TAR en los gastos sanitarios de los pacientes en Eswatini. Catorce centros sanitarios fueron asignados aleatoriamente a la transición en uno de los siete periodos de la asistencia estándar (elegibilidad para la TAR en niveles definidos de recuento de CD4) a la intervención de TAR inmediato para todos (EAAA). Se entrevistó a 2.261 pacientes con VIH a lo largo del estudio para conocer sus gastos sanitarios del año anterior. Según los modelos de regresión de efectos mixtos, se observó un descenso del 49% (RR: 0,51; IC del 95%: 0,36, 0,72; p<0,001) en el gasto sanitario total del año anterior en el grupo de la EAAA, y un descenso del 98% (RR 0,02; IC del 95%: 0,00, 0,02; p<0,001) en el gasto en asistencia sanitaria privada y tradicional. A pesar de una mayor frecuencia de visitas deatención de VIH para los pacientes que recién comenzaron laTAR, la aplicación inmediata de laTAR redujo los gastos sanitarios de los pacientes dado que buscaron menos atención de proveedores de asistencia sanitaria alternativos. Este estudio añade un importante argumento económico a la recomendación de la Organización Mundial de la Salud de abolir las restricciones de elegibilidad para la terapia antirretroviral basados en el recuento de CD4.
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Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Esuatini , Infecciones por VIH/tratamiento farmacológico , Gastos en Salud , HumanosRESUMEN
BACKGROUND: Glycosaminoglycans (GAGs) are negatively charged long linear (highly sulfated) polysaccharides consisting of repeating disaccharide units that are expressed on the surfaces of all nucleated cells. The expression of GAGs is required for embryogenesis, regulation of cell growth and proliferation, maintenance of tissue hydration, and interactions of the cells via receptors. Mucopolysaccharidoses (MPS) are caused by deficiency of specific lysosomal enzymes that result in the accumulation of GAGs in multiple tissues leading to organ dysfunction. Therefore, GAGs are important biomarkers for MPS. Without any treatment, patients with severe forms of MPS die within the first two decades of life. SCOPE OF REVIEW: Accurate measurement of GAGs is important to understand the diagnosis and pathogenesis of MPS and to monitor therapeutic efficacy before, during, and after treatment of the disease. This review covers various qualitative and quantitative methods for measurement of GAGs, including dye specific, thin layer chromatography (TLC), capillary electrophoresis, high-performance liquid chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-MS/MS), gas chromatography, ELISA, and automated high-throughput mass spectrometry. Major conclusion: There are several methods for GAG detection however, specific GAG detection in the various biological systems requires rapid, sensitive, specific, and cost-effective methods such as LC-MS/MS. GENERAL SIGNIFICANCE: This review will describe different methods for GAG detection and analysis, including their advantages and limitation.
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Biomarcadores/metabolismo , Glicosaminoglicanos/metabolismo , Mucopolisacaridosis/diagnóstico , Humanos , Mucopolisacaridosis/metabolismoRESUMEN
Mucopolysaccharidosis type I (MPS-I), a lysosomal storage disorder caused by a deficiency of alpha-L-iduronidase enzyme, results in the progressive accumulation of glycosaminoglycans and consequent multiorgan dysfunction. Despite the effectiveness of hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) in correcting clinical manifestations related to visceral organs, complete improvement of musculoskeletal and neurocognitive defects remains an unmet challenge and provides an impact on patients' quality of life. We tested the therapeutic efficacy of combining HSCT and ERT in the neonatal period. Using a mouse model of MPS-I, we demonstrated that the combination therapy improved clinical manifestations in organs usually refractory to current treatment. Moreover, combination with HSCT prevented the production of anti-IDUA antibodies that negatively impact ERT efficacy. The added benefits of combining both treatments also resulted in a reduction of skeletal anomalies and a trend towards decreased neuroinflammation and metabolic abnormalities. As currently there are limited therapeutic options for MPS-I patients, our findings suggest that the combination of HSCT and ERT during the neonatal period may provide a further step forward in the treatment of this rare disease.
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Remodelación Ósea , Modelos Animales de Enfermedad , Terapia de Reemplazo Enzimático/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Iduronidasa/fisiología , Mucopolisacaridosis I/terapia , Animales , Animales Recién Nacidos , Terapia Combinada , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mucopolisacaridosis I/enzimología , Mucopolisacaridosis I/patologíaRESUMEN
Porous carbon nanosheets have the advantages of longitudinal continuity, transverse ultrathin, high specific surface area, and surface atomic activity, as well as the synergistic effect of micro and nanoproperties, so the research on their preparation, structure, and properties has attracted wide attention. A series of ultrathin hierarchical porous carbon nanosheets (HPCNs) is fabricated through carbonization of precursors obtained through the Friedel-Crafts reaction-assisted loading of polystyrene on graphene oxide. Hierarchical pore structures consist of three parts: (1) the micropores (1.3 nm), which were provided by porous polystyrene through the Friedel-Crafts reaction; (2) the mesopores (3.8 nm), which were provided by slab pores from the stack of carbon nanosheets; and (3) the pores (>5 nm) formed from the random stack of carbon nanosheets. Controlling the carbonization time and temperature adds to a prominent increase in specific surface area from 405.8 to 1420 m2 g-1. It was found that excessive carbonization would destroy the hierarchical pore structure. These porous carbon materials were used as cathode materials for lithium-sulfur battery and showed good performance. HPCN/sulfur cathode has good rate performance and cycle performance, and the capacity retention rate is 87% after the current density rises from 1 to 3 C and 91% after 200 cycles.
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PURPOSE OF REVIEW: The MaxART Consortium-led by the Eswatini Ministry of Health-implemented multiple interventions between 2012 and 2017 to achieve UNAIDS 90-90-90 targets. We summarize key findings from community outreach strategies in support of the first 90 goal, and from the Early Access to ART for All (EAAA) trial on the implementation of a "Treat All" strategy to achieve the second and third 90 goals within a government-managed public health system. RECENT FINDINGS: The MaxART Consortium demonstrated that "Fast Track," a problem-solving approach, was effective at increasing testing coverage in the community. Compared with baseline data at 3 months prior to the start of the Fast Track, there was a 273% proportional increase in HIV tests conducted among adolescent males, adolescent females, and adult men, and 722% over baseline for adolescent males. The MaxART EAAA trial further showed that implementation of the Treat All policy was associated with significant two-fold shorter time from enrollment into care to ART initiation than under the standard CD4+ cell threshold-based treatment guidelines. Finally, through the MaxART trial, Eswatini was able to identify areas for further investment, including addressing the system-side barriers to routine viral load monitoring, and designing and implementing innovative community-based approaches to reach individuals who were not more routinely accessing HIV testing and counseling services. As low- and middle-income countries adopt the Treat All approach in their national HIV care and treatment guidelines, further implementation science research is needed to understand and address the system-level barriers to achieving the benefits of Treat All for HIV-infected individuals and those at risk.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Tamizaje Masivo/métodos , Adolescente , Adulto , Protocolos Clínicos , Relaciones Comunidad-Institución , Consejo , Esuatini , Femenino , Humanos , Masculino , Carga ViralRESUMEN
Mucolipidosis II and III (ML II/III) are caused by a deficiency of uridine-diphosphate N-acetylglucosamine: lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. The process is performed by a sequential two-step process: first, GlcNAc-1-phosphotransferase catalyzes the transfer of GlcNAc-1-phosphate to the selected mannose residues on lysosomal enzymes in the cis-Golgi network. The second step removes GlcNAc from lysosomal enzymes by N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (uncovering enzyme) and exposes the mannose 6-phosphate (M6P) residues in the trans-Golgi network, in which the enzymes are targeted to the lysosomes by M6Preceptors. A deficiency of GlcNAc-1-phosphotransferase causes the hypersecretion of lysosomal enzymes out of cells, resulting in a shortage of multiple lysosomal enzymes within lysosomes. Due to a lack of GlcNAc-1-phosphotransferase, the accumulation of cholesterol, phospholipids, glycosaminoglycans (GAGs), and other undegraded substrates occurs in the lysosomes. Clinically, ML II and ML III exhibit quite similar manifestations to mucopolysaccharidoses (MPSs), including specific skeletal deformities known as dysostosis multiplex and gingival hyperplasia. The life expectancy is less than 10 years in the severe type, and there is no definitive treatment for this disease. In this review, we have described the updated diagnosis and therapy on ML II/III.
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Terapia de Reemplazo Enzimático/métodos , Terapia Genética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Lisosomas/metabolismo , Mucolipidosis/diagnóstico , Animales , Transporte Biológico Activo , Modelos Animales de Enfermedad , Glicosaminoglicanos/metabolismo , Humanos , Manosafosfatos/metabolismo , Mucolipidosis/enzimología , Mucolipidosis/fisiopatología , Mucolipidosis/terapiaRESUMEN
Allogenic hematopoietic stem cell transplantation (HSCT) has proven to be a viable treatment option for a selected group of patients with mucopolysaccharidoses (MPS), including those with MPS types I, II, IVA, VI, and VII. Early diagnosis and timely referral to an expert in MPS are critical, followed by a complete examination and evaluation by a multidisciplinary team, including a transplantation physician. Treatment recommendations for MPS are based on multiple biological, sociological, and financial factors, including type of MPS, clinical severity, prognosis, present clinical signs and symptoms (disease stage), age at onset, rate of progression, family factors and expectations, financial burden, feasibility, availability, risks and benefits of available therapies such as HSCT, enzyme replacement therapy (ERT), surgical interventions, and other supportive care. International collaboration and data review are critical to evaluating the therapeutic efficacy and adverse effects of HSCT for MPS. Collaborative efforts to assess HSCT for MPS have been ongoing since the first attempt at HSCT in a patient with MPS reported in 1981. The accumulation of data since then has made it possible to identify early outcomes (ie, transplantation outcomes) and long-term disease-specific outcomes resulting from HSCT. The recent identification of predictive factors and the development of innovative regimens have significantly improved the outcomes of both engraftment failure and transplantation-related mortality. Assessment of long-term outcomes has considered a variety of factors, including type of MPS, type of graft, age at transplantation, and stage of disease progression, among others. Studies on long-term outcomes are considered a key factor in the use of HSCT in patients with MPS. These studies have shown the effects and limitations of HSCT on improving disease manifestations and quality of life. In this review, we summarize the efficacy, side effects, risks, and cost of HSCT for each type of MPS.
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Trasplante de Células Madre Hematopoyéticas/historia , Mucopolisacaridosis/historia , Mucopolisacaridosis/terapia , Aloinjertos , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
INTRODUCTION: There are concerns that immediate ART initiation (regardless of CD4 count) negatively affects HIV status disclosure, ART adherence and healthcare interactions. We assessed changes in these factors after the 'Early access to ART for all' intervention, a universal test-and-treat study in Swaziland. METHODS: We recruited two samples of participants between 2014 and 2017. The first group was interviewed before the intervention (control); the second group at the implementation and 6 months thereafter (intervention). RESULTS: High levels of disclosure to partners (controls and intervention: 94%) and family members (controls: 78%, intervention: 79%) were reported, and high levels of adherence (85% did not miss a dose among the controls, 84% in the intervention group). There were no changes in patients reporting feeling pressured to initiate ART (controls: 10%, intervention: 11%). The quality of interaction with healthcare workers improved after the intervention; healthcare workers explained more often the choice of ART initiation (controls: 88%, intervention: 93%) and the meaning of both CD4 and viral load test results (controls: 15%, intervention: 47%). More patients in the intervention group reported receiving test results (controls: 13%, intervention: 46%). We observed no changes in disclosure, adherence or patient experiences 6 months into the intervention compared to its start. CONCLUSION: Our results suggest that both reported adherence and disclosure levels remain high after the introduction of immediate ART in Swaziland. We observed an improvement in the healthcare interactions, possibly due to training at participating facilities, which will be an important element for a successful roll-out of immediate ART.
OBJECTIF: Il y a des craintes que l'initiation de l'ART immédiat (quel que soit la numération des CD4) affecte négativement la divulgation du statut VIH, l'adhésion au traitement et les interactions avec les soins de santé. Nous avons évalué les modifications de ces facteurs après l'intervention «Accès précoce à l'ART pour tous¼, une étude universelle de dépistage et traitement au Swaziland. MÉTHODES: Nous avons recruté deux échantillons de participants entre 2014 et 2017. Le premier groupe a été interviewé avant l'intervention (témoins), le deuxième groupe lors de l'implémentation et six mois après (intervention). RÉSULTATS: Des niveaux élevés de divulgation aux partenaires (témoin et intervention: 94%) et aux membres de la famille (témoins: 78%, intervention: 79%) ont été rapportés, ainsi que des taux élevés d'adhésion (85% n'ont pas oublié une dose chez les témoins, 84% dans le groupe d'intervention). Aucun changement n'a été observé chez les patients déclarant se sentir poussés à commencer l'ART (témoins: 10%, intervention: 11%). La qualité de l'interaction avec les agents de la santé s'est améliorée après l'intervention; les agents de santé expliquent plus souvent le choix de l'initiation de l'ART (témoins: 88%, intervention: 93%) et la signification des résultats des tests de CD4 et de la charge virale (témoins: 15%, intervention: 47%). Plus de patients du groupe d'intervention ont déclaré avoir reçu les résultats des tests (témoins: 13%, intervention: 46%). Nous n'avons observé aucun changement dans la divulgation, l'adhésion ou l'expérience des patients six mois après le début de l'intervention par rapport à son début. CONCLUSION: Nos résultats suggèrent que les taux d'adhésion et de divulgation rapportés restent élevés après l'introduction de l'ART immédiat au Swaziland. Nous avons observé une amélioration des interactions avec les soins de santé, probablement due à la formation dispensée dans les établissements participants, ce qui constituera un élément important pour le succès du déploiement de l'ART immédiat.
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Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Revelación , Familia , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación , Parejas Sexuales , Adulto , Esuatini , Femenino , Personal de Salud , Accesibilidad a los Servicios de Salud , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Relaciones Profesional-Paciente , Carga ViralRESUMEN
To explore the correlation between glycosaminoglycan (GAG) levels and mucopolysaccharidosis (MPS) type, we have evaluated the GAG levels in blood of MPS II, III, IVA, and IVB and urine of MPS IVA, IVB, and VI by tandem mass spectrometry. Dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS; mono-sulfated KS, di-sulfated KS), and the ratio of di-sulfated KS in total KS were measured. Patients with untreated MPS II had higher levels of DS and HS in blood while untreated MPS III had higher levels of HS in blood than age-matched controls. Untreated MPS IVA had higher levels of KS in blood and urine than age-matched controls. The ratio of blood di-sulfated KS/total KS in untreated MPS IVA was constant and higher than that in controls for children up to 10â¯years of age. The ratio of urine di-sulfated KS/total KS in untreated MPS IVA was also higher than that in age-matched controls, but the ratio in untreated MPS IVB was lower than controls. ERT reduced blood DS and HS in MPS II, and urine KS in MPS IVA patients, although GAGs levels remained higher than the observed in age-matched controls. ERT did not change blood KS levels in MPS IVA. MPS VI under ERT still had an elevation of urine DS level compared to age-matched controls. There was a positive correlation between blood and urine KS in untreated MPS IVA patients but not in MPS IVA patients treated with ERT. Blood and urine KS levels were secondarily elevated in MPS II and VI, respectively. Overall, measurement of GAG levels in blood and urine is useful for diagnosis of MPS, while urine KS is not a useful biomarker for monitoring therapeutic efficacy in MPS IVA.